Shari Al, BSc, MSc

Alzheimer's Disease (AD) is defined as a disorder characterized by the progressive deterioration of mental function. Specific research into the genetics of this disease has recently uncovered several important details as to the pathology and progression of the disorder. These discoveries, in turn, may lead to improved diagnosis and/or treatment of AD, with obvious repercussions for clinicians. In the case of AD genetic heterogeneity and the discovery that variations at any one of several loci cause the same disease, initially made it difficult for researchers to progress. The table below summarizes the results of current genetic research showing which genes are linked to each specific type of AD, and the percentage of patients affected by each type.

Andrea Sotirakopoulos, BSc

Gonadal steroids have wide and complex roles that reach beyond the regulation of gonadotrophin and prolactin secretion and the modulation of sexual behavior.¹ These hormones have several clinical effects on brain function throughout the life span, beginning during gestation and continuing into senescence. Estrogen is a female steroid hormone that is produced in the ovary and circulates in the blood stream. The specific proteins that bind to estrogen are distributed throughout the limbic brain, forebrain, hypothalamus, midbrain and anterior pituitary, and in organs such as the ovary and uterus. The widespread hormonal influence of estrogen on brain function could prove to be an important tool in the fight against Alzheimer's Disease (AD).

AD is characterized by neuropathologic features such as the accumulation of neurofibrillary tangles, neuritic plaques and amyloid deposits within regions of the cerebrum and brainstem² and by the progressive decline of mental function affecting long-term memory and other cognitive domains.³ A close relationship between neurofibrillary tangles and cell death exists within the brains of patients with AD. In the cholinergic basal forebrain and the hippocampus, these tangles are found inside neurons of cell groups that are progressively depopulated.

Barry J. Goldlist, MD, FRCPC, FACP

Diseases that affect the brain have a special horror for people of any age. A person who has suffered a heart attack might be very ill, might even die, but the disease does not alter the 'essence' of the individual. They are recognizably the same people they were before their illness. The same is not true of diseases that affect the brain. Our intellect, our communication skills, our emotions, define us as human beings and differentiate us from other creatures and also from each other.

The two great scourges of old age are stroke and Alzheimer's Disease (AD): they rob individuals not only of their health but also of that very 'essence' of individual humanity. Over the last four decades, enormous strides have been made in our ability to prevent stroke. The pillars of this advance have been aspirin and carotid endarterectomy for TIA's and strokes, control of hypertension, and anticoagulation for atrial fibrillation. Further progress is likely when the correct place for lipid lowering medication and homocysteine lowering maneuvers are better understood in the elderly.

Unfortunately, the story for the prevention and treatment of AD has so far not been as favorable. For many years the very term 'senile dementia' itself has been an impediment to research. Many physicians, and much of the general public, assumed it was an inevitable part of aging, and therefore not amenable to any therapy. This despite the fact that the majority of elderly do not develop cognitive impairment that impairs function, even at very advanced ages. Only a few scientists devoted themselves to research in AD (one notable example being Donald McLachlan at the University of Toronto, who was awarded the Order of Canada for his contributions).

This lack of interest has changed dramatically over the past few years. Part of the 'push' towards research has been the changing demography of developed nations. A larger proportion of the population is over 65, and the segment of the population over 80 is the fastest growing segment of society. The Canadian Study on Health and Aging has suggested that up to a third of this group over 80 will develop cognitive impairment severe enough to warrant the diagnosis of dementia. Dementia is the most common reason for long term institutionalization of the elderly, so the human tragedy of this disease is now compounded by economic pressures.

As is the case in most medical advances, the key to any successes in understanding AD - that lead to treatment or prevention - lies in basic research. The original wave of scientific discoveries in AD highlighted some of the biochemical deficiencies, and has led to the current therapeutic strategy of cholinesterase inhibition in patients with the disease. An even more fundamental understanding of the disorder is likely to come from understanding the molecular biology of the disease. Already, several genes linked to Alzheimer's Disease have been identified. It is hoped that this represents the first step in unraveling the actual pathogenesis of the disease, and thus identifying possible preventive and therapeutic options.

As the disease becomes a more popular one for scientific research, more and more information is becoming available. The present wave of correlations discovered by epidemiological research have to be viewed cautiously. Certainly, the preventive possibilities of estrogen and non-steroidal anti inflammatory drugs are very exciting, but not yet at the stage where they can be prescribed for that indication. Similarly the literature on anti-oxidants, ginkgo biloba, and other substances is not yet solid enough to warrant routine therapy.

It is also important to remember that meticulous attention to concurrent illnesses (medical and psychiatric) can result in dramatic and sustained functional improvements in demented individuals, even though the underlying dementing process is not altered. As well, attention to caregiver support can be as effective in maintaining demented individuals at home as any of the current medications in our growing armamentarium.

Alzheimer's Disease, the scourge of old age, is not yet truly amenable to medical intervention. However, for the first time since its description, a reasonable expectation of progress is finally here. It is certainly an exciting time to be involved in the research surrounding this challenging illness.

Thomas Tsirakis, BA

Alzheimer Disease (AD) is the leading cause of dementia in Canada, affecting 8% of the general population over 60 years of age, and more than 35% of those over 80 years of age. The current number of Canadians affected with the disease is estimated to be 160,000 with approximately 10,000 dying of AD and related dementias every year.

The normal progression of AD typically follows a gradual 7- to 10-year decline in cognitive abilities. All brain functions are eventually affected, but disturbances in judgment, memory, and language appear early on in the disease, with motor function, and bowel and bladder control being maintained during this time period. The progressive and slow decline of an individual's cognitive abilities in AD has been compared to observing the process of normal human development in a reverse order.

Since there is currently no definitive clinical test available for establishing the presence of AD, it is imperative that the clinician utilize standardized diagnostic criteria and formal testing in order to rule out the possibility of any reversible forms of dementia. Individuals presenting with cognitive deficits of a rapid onset should be suspected of having some underlying etiology other than AD.